Membrane transport free energy

Thiazide diuretics inhibit NaCl transport in the DCT the proximal tubule may be a secondary site of action. Figure 28-4 illustrates the current model of electrolyte transport in the DCT. Transport is powered by a Na pump in the basolateral membrane. The free energy in the electrochemical gradient for Na is harnessed by a Na -CT symporter in the luminal membrane that moves Ct into the epithelial cell against its electrochemical gradient. Ct then exits the basolateral membrane passively via a Ct channel. Thiazide diuretics inhibit the Na -Ct symporter (Figure 28-4). 

Electrons from cytochrome c are first transferred to the binuclear Cua center which displays a delocalized mixed-valence (Cu(1.5)-Cu(1.5)) electronic structure in its oxidized state (see Chapter 8.4). Heme Fe is also another electron transfer center that is believed to be in rapid redox equilibrium with Cub. Subsequent electron transfer occurs to subunit I and the binuclear heme As-Cub center, where molecular oxygen reduction occurs. During this process, four protons are supplied from the inner membrane. The free energy made available by this exergonic reaction drives the translocation ( pump ) of four additional protons per O2 molecule reduced from the IN side to the OUT side. The active transport of protons generates an electrochemical gradient across the membrane that ultimately drives ATP synthesis. 

Passive diffusion is the simplest transport process. In passive diffusion, the transported species moves across the membrane in the thermodynamically favored direction without the help of any specific transport system/molecule. For an uncharged molecule, passive diffusion is an entropic process, in which movement of molecules across the membrane proceeds until the concentration of the substance on both sides of the membrane is the same. For an uncharged molecule, the free energy difference between side 1 and side 2 of a membrane (Figure 10.1) is given by... 

Fructose is present outside a cell at 1 /iM concentration. An active transport system in the plasma membrane transports fructose into this cell, using the free energy of ATP hydrolysis to drive fructose uptake. Assume that one fructose is transported per ATP hydrolyzed, that ATP is hydrolyzed on the intracellular surface of the membrane, and that the concentrations of ATP, ADP, and Pi are 3 mM, 1 mM, and 0.5 mM, respectively. T = 298 K. What is the highest intracellular concentration of fructose that this transport system can generate Hint Kefer to Chapter 3 to recall the effects of concentration on free energy of ATP hydrolysis.)... 

This chapter describes some of the properties of solids that affect transport across phases and membranes, with an emphasis on biological membranes. Four aspects are addressed. They include a comparison of crystalline and amorphous forms of the drug, transitions between phases, polymorphism, and hydration. With respect to transport, the major effect of each of these properties is on the apparent solubility, which then affects dissolution and consequently transport. There is often an opposite effect on the stability of the material. Generally, highly crystalline substances are more stable but have lower free energy, solubility, and dissolution characteristics than less crystalline substances. In some situations, this lower solubility and consequent dissolution rate will result in reduced bioavailability. 

Methods similar to those discussed in this chapter have been applied to determine free energies of activation in enzyme kinetics and quantum effects on proton transport. They hold promise to be coupled with QM/MM and ab initio simulations to compute accurate estimates of nulcear quantum effects on rate constants in TST and proton transport rates through membranes. 

Taft equation (eq 16 in reference (36)) and reverse osmosis data on solute transport parameter Dam/K6 (defined by eq 12 later in this discussion) for different solutes and membranes (44,45,46), and (iv) the functional similarity of the thermodynamic quantity AAF+ representing the transition state free energy change (36) and the quantity AAG defined as... 

Carrier-mediated passage of a molecular entity across a membrane (or other barrier). Facilitated transport follows saturation kinetics ie, the rate of transport at elevated concentrations of the transportable substrate reaches a maximum that reflects the concentration of carriers/transporters. In this respect, the kinetics resemble the Michaelis-Menten behavior of enzyme-catalyzed reactions. Facilitated diffusion systems are often stereo-specific, and they are subject to competitive inhibition. Facilitated transport systems are also distinguished from active transport systems which work against a concentration barrier and require a source of free energy. Simple diffusion often occurs in parallel to facilitated diffusion, and one must correct facilitated transport for the basal rate. This is usually evident when a plot of transport rate versus substrate concentration reaches a limiting nonzero rate at saturating substrate While the term passive transport has been used synonymously with facilitated transport, others have suggested that this term may be confused with or mistaken for simple diffusion. See Membrane Transport Kinetics... 

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